Improving the accuracy of model-based quantitative nuclear magnetic resonance

Abstract

Low spectral resolution and extensive peak overlap are the common challenges that preclude quantitative analysis of nuclear magnetic resonance (NMR) data with the established peak integration method. While numerous model-based approaches overcome these obstacles and enable quantification, they intrinsically rely on rigid assumptions about functional forms for peaks, which are often insufficient to account for all unforeseen imperfections in experimental data. Indeed, even in spectra with well-separated peaks whose integration is possible, model-based methods often achieve suboptimal results, which in turn raises the question of their validity for more challenging datasets. We address this problem with a simple model adjustment procedure, which draws its inspiration directly from the peak integration approach that is almost invariant to lineshape deviations. Specifically, we assume that the number of mixture components along with their ideal spectral responses are known; we then aim to recover all useful signals left in the residual after model fitting and use it to adjust the intensity estimates of modelled peaks. We propose an alternative objective function, which we found particularly effective for correcting imperfect phasing of the data – a critical step in the processing pipeline. Application of our method to the analysis of experimental data shows the accuracy improvement of 20 %–40 % compared to the simple least-squares model fitting.